CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease

Although in vitro studies suggest that neutralization by monoclonal antibodies (mAbs) against SARS CoV2 Omicron sub lineages is reduced, in vivo virological response data are lacking. MONET (EudraCT: 2021-004188-28) was multi-centric phase 4 open-label parallel randomized clinical trial, conducted in Italy over 2022-2023, to assess the efficacy of sotrovimab (SOT), tixagevimab/cilgavimab (TIX/CIL) and Nirmatrelvir/ritonavir (NMV/r), in outpatients at high risk for severe COVID-19. The outcome (secondary in the trial protocol) was SARS-CoV-2 variation in cycle threshold (CT) values over the first 7 days (D1-D7) of the trial. CT variation was compared by trial arms using unadjusted linear regression and after controlling for age. We included 346 individuals: 116 (34%) received SOT, 113 (33%) TIX/CIL, 117 (34%) NMV/r. Main characteristics were balanced across arms. Most of the participants were infected with BA.2 (52%) or BA.4/5 (35.5%). The data carried strong evidence that the mean CT change over D1-D7 was larger in subjects receiving NMV/r vs. the other arms (p < 0.001). We found no evidence that viral variant was an effect measure modifier for the contrasts of interest (p = 0.14). Our analysis provides strong evidence that NMV/r exerts a greater in vivo antiviral effect than anti-Spike mAbs against Omicron sub lineages, confirming previous in vitro data.

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Journal
Scientific Reports
Published
2025-08-18
DOI
https://doi.org/10.1038/s41598-025-15641-1
Primary Topic
COVID-19 Clinical Research Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease

Roberto Cauda, Francesca Colavita, Miriam Lichtner, Marcello Tavio et al.
Scientific Reports
COVID-19 Clinical Research Studies
article

CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease

Roberto Cauda, Francesca Colavita, Miriam Lichtner, Marcello Tavio, Giulia Berno, Pietro Vittozzi, Eliana Specchiarello, Angela Corpolongo, Massimo Puoti, Enrico Girardi, Paolo Grossi, Ilaria Mastrorosa, Carlotta Cerva, Martina Rueca, Emanuela Giombini, Francesca Faraglia, Pierluigi Blanc, Claudio Maria Mastroianni, Laura Scorzolini, Anna Maria Cattelan, Alessandra Oliva, Fabrizio Maggi, Samir Al Moghazi, Francesca Gavaruzzi, Silvia Meschi, Emanuele Nicastri, Serena Vita, Federico De Zottis, Chiara Iaria, Alessandra D’Abramo, Cesare Ernesto Maria Gruber, Antonio Cascio, Alessandra Vergori, Massimo Andreoni, Valentina Mazzotta, Roberto Parrella, Emanuela Caraffa, Laura Loiacono, Silvia Di Bari, Davide Roberto Donno, Raffaele Bruno, Carlo Torti, Giulia Matusali, Carmelo Iacobello, Annalisa Saracino, Cristina Mussini, Marco Massari, Ivan Gentile, Elisa Biliotti, Eugenia Milozzi, Fabrizio Carletti, Marco Libanore, Massimo Di Pietro, Giuliano Rizzardini, Andrea Gori, Giovanni Di Perri, Simone Lanini, Maria Letizia Giancola, Andrea Mariano, Andrea Antinori, Pierluigi Viale, Silvia Rosati, Raffaella Libertone, Alessandro Cozzi‐Lepri, Nazario Bevilacqua
article en

Abstract

Although in vitro studies suggest that neutralization by monoclonal antibodies (mAbs) against SARS CoV2 Omicron sub lineages is reduced, in vivo virological response data are lacking. MONET (EudraCT: 2021-004188-28) was multi-centric phase 4 open-label parallel randomized clinical trial, conducted in Italy over 2022-2023, to assess the efficacy of sotrovimab (SOT), tixagevimab/cilgavimab (TIX/CIL) and Nirmatrelvir/ritonavir (NMV/r), in outpatients at high risk for severe COVID-19. The outcome (secondary in the trial protocol) was SARS-CoV-2 variation in cycle threshold (CT) values over the first 7 days (D1-D7) of the trial. CT variation was compared by trial arms using unadjusted linear regression and after controlling for age. We included 346 individuals: 116 (34%) received SOT, 113 (33%) TIX/CIL, 117 (34%) NMV/r. Main characteristics were balanced across arms. Most of the participants were infected with BA.2 (52%) or BA.4/5 (35.5%). The data carried strong evidence that the mean CT change over D1-D7 was larger in subjects receiving NMV/r vs. the other arms (p < 0.001). We found no evidence that viral variant was an effect measure modifier for the contrasts of interest (p = 0.14). Our analysis provides strong evidence that NMV/r exerts a greater in vivo antiviral effect than anti-Spike mAbs against Omicron sub lineages, confirming previous in vitro data.

Scientific ReportsVol. 15(1)
University of Insubria (IT), University of Rome Tor Vergata (IT), University of Udine (IT), University of Padua (IT), University of Ferrara (IT), Ospedale del Ceppo (IT), Agostino Gemelli University Polyclinic (IT), National Institute for Health and Care Research (GB), Luigi Sacco Hospital (IT), Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (IT), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), National Centre for Disease Prevention and Control (IT), IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT), Ospedali Riuniti di Ancona (IT), Azienda Ospedaliero Universitaria Ospedali Riuniti (IT), Azienda Ospedaliero-Universitaria di Modena (IT), Ospedale Amedeo di Savoia (IT), Federico II University Hospital (IT), Azienda Ospedaliera Sant'Andrea (IT), Ospedale Cannizzaro (IT), Azienda di Rilievo Nazionale ed Alta Specializzazione (IT), Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone" di Palermo (IT), Ospedale D. Cotugno (IT), Policlinico San Matteo Fondazione (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Azienda Usl Toscana Centro (IT), St. Anna Hospital (DE), ASST Fatebenefratelli Sacco (IT), University College London (GB), University of Bari Aldo Moro (IT), University of Naples Federico II (IT), Sapienza University of Rome (IT), University of Bologna (IT)
HORIZON EUROPE Framework Programme
Openalex Percentile: Top 74%
COVID-19 Clinical Research Studies
DOIOpen Access PDFOpenAlex
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